Sculpting the immune response to infection.

Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
Nature Immunology (Impact Factor: 26.2). 01/2011; 12(7):579-82. DOI:10.1038/ni0711-579
Source: PubMed
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    ABSTRACT: The mucosal surfaces of fish serve as the first line of defense against the myriad of aquatic pathogens present in the aquatic environment. The immune repertoire functioning at these interfaces is still poorly understood. The skin, in particular, must process signals from several fronts, sensing and integrating environmental, nutritional, social, and health cues. Pathogen invasion can disrupt this delicate homeostasis with profound impacts on signaling throughout the organism. Here, we investigated the transcriptional effects of virulent Aeromonas hydrophila infection in channel catfish skin, Ictalurus punctatus. We utilized a new 8 x 60K Agilent microarray for catfish to examine gene expression profiles at critical early timepoints following challenge-2 h, 8 h, and 12 h. Expression of a total of 2,168 unique genes was significantly perturbed during at least one timepoint. We observed dysregulation of genes involved in antioxidant, cytoskeletal, immune, junctional, and nervous system pathways. In particular, A. hydrophila infection rapidly altered a number of potentially critical lectins, chemokines, interleukins, and other mucosal factors in a manner predicted to enhance its ability to adhere to and invade the catfish host.
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    ABSTRACT: Bacterial pathogens are well-equipped to detect, adhere to, and initiate infection in their finfish hosts. The mucosal surfaces of fish, such as the skin, function as the front line of defense against such bacterial insults that are routinely encountered in the aquatic environment. While recent progress has been made, and despite the obvious importance of mucosal surfaces, the precise molecular events that occur soon after encountering bacterial pathogens remain unclear. Indeed, these early events are critical in mounting appropriate responses that ultimately determine host survival or death. In the present study, we investigated the transcriptional consequences of a virulent A. hydrophila challenge in the skin of blue catfish, Ictalurus furcatus. We utilized an 8X60K Agilent microarray to examine gene expression profiles at key early timepoints following challenge (2 h, 12 h, and 24 h). A total of 1,155 unique genes were significantly altered during at least one timepoint. We observed dysregulation in a number of genes involved in diverse pathways including those involved in antioxidant responses, apoptosis, cytoskeletal rearrangement, immunity, and extracellular matrix protein diversity and regulation. Taken together, A. hydrophila coordinately modulates mucosal factors across numerous cellular pathways in a manner predicted to enhance its ability to adhere to and infect the blue catfish host.
    Fish &amp Shellfish Immunology 01/2013; · 2.96 Impact Factor
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    ABSTRACT: Dendritic cells (DCs) are professional antigen-presenting cells that play a critical role to activate immune response. They may be targeted for immunomodulation by microbes, including probiotics. In this study, chicken bone marrow dendrite cells (chi-BMDCs) were stimulated with lipopolysachride (LPS), Saccharomyces boulardii (Sb), Bacillus subtilis B10 (Bs), co-culture of Sb + Bs and phosphate buffer saline (PBS) as a control group (Ctr) at 3 h, 6 h and 12 h intervals. Results revealed that treatment groups modulated the phenotype and biological functions of chi-BMDCs. Scan electron microscopy showed attachment of probiotics on the surface of chi-BMDCs. Additionally transmission electron microscopy (TEM) revealed efficiently engulfing and degradation of probiotics. Gene expression levels of MHC-II, CD40, CD80 and CD86 up-regulated in stimulated groups. Furthermore, toll-like receptors TLR1, TLR2, TLR4 and chicken specific TLR15 expressions were improved and downstream associated factors MyD88, TRAF6, TAB1 and NFκ-B mRNA levels increased in all treatment groups as compared to control. Surprisingly, NFκ-B response was noted significant higher in LPS treatment among all groups. Moreover, IL-1β, IL-17, IL-4, TGF-β and IL-10 production levels were found higher, and lower concentration of INF-γ and IL-8 were observed in Sb, Bs and Sb + Bs treatment groups. In contrast, LPS groups showed prominent increase in IL-12, INF-γ and IL-8 concentration levels as compared to control group. Altogether, these results emphasize a potentially important role of Saccharomyces boulardii and Bacillus subtilis B10 in modulating immunological functions of chi-BMDCs by targeting specific toll like receptors (TLRs) and associated factors. The role of probiotics on chi-BMDCs functionality in a non-mammalian species have been presented for the first time. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.
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